An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides

Wael E. Houssen; Andrew F. Bent; Andrew R. McEwan; Nathalie Pieiller; Jioji Tabudravu; Jesko Koehnke; Greg Mann; Rosemary I. Adaba; Louise Thomas; Usama W. Hawas; Huanting Liu; Ulrich Schwarz-Linek; Margaret C. M. Smith; James H. Naismith; Marcel Jaspars

doi:10.1002/anie.201408082

An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides

Wael E. Houssen, Andrew F. Bent, Andrew R. McEwan, Nathalie Pieiller, Jioji Tabudravu, Jesko Koehnke, Greg Mann, Rosemary I. Adaba, Louise Thomas, Usama W. Hawas, Huanting Liu, Ulrich Schwarz-Linek, Margaret C. M. Smith, James H. Naismith^*, Marcel Jaspars^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.

Original language	English
Pages (from-to)	14171-14174
Number of pages	4
Journal	Angewandte Chemie International Edition
Volume	53
Issue number	51
Early online date	21 Oct 2014
DOIs	https://doi.org/10.1002/anie.201408082
Publication status	Published - 15 Dec 2014

Keywords

cyanobactins
cyclic peptides
biosynthesis
patellamides
ribosomal peptides
discovery
macrocyclization
route

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/anie.201408082Licence: CC BY

Houssen_et_al-2014-Angewandte_Chemie_International_Edition
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Final published version, 479 KBLicence: CC BY

Marcel Jaspars
- Coastal Communities
- Engineering, National Decommissioning Centre
- School of Natural & Computing Sciences, Chemistry - Chair in Chemistry
Person: Academic

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Houssen, W. E., Bent, A. F., McEwan, A. R., Pieiller, N., Tabudravu, J., Koehnke, J., Mann, G., Adaba, R. I., Thomas, L., Hawas, U. W., Liu, H., Schwarz-Linek, U., Smith, M. C. M., Naismith, J. H., & Jaspars, M. (2014). An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides. Angewandte Chemie International Edition, 53(51), 14171-14174. https://doi.org/10.1002/anie.201408082

Houssen, WE, Bent, AF, McEwan, AR, Pieiller, N, Tabudravu, J, Koehnke, J, Mann, G, Adaba, RI, Thomas, L, Hawas, UW, Liu, H, Schwarz-Linek, U, Smith, MCM, Naismith, JH & Jaspars, M 2014, 'An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides', Angewandte Chemie International Edition, vol. 53, no. 51, pp. 14171-14174. https://doi.org/10.1002/anie.201408082

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title = "An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides",

abstract = "Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.",

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AU - Tabudravu, Jioji

AU - Koehnke, Jesko

AU - Mann, Greg

AU - Adaba, Rosemary I.

AU - Thomas, Louise

AU - Hawas, Usama W.

AU - Liu, Huanting

AU - Schwarz-Linek, Ulrich

AU - Smith, Margaret C. M.

AU - Naismith, James H.

AU - Jaspars, Marcel

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AB - Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.

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KW - biosynthesis

KW - patellamides

KW - ribosomal peptides

KW - discovery

KW - macrocyclization

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JF - Angewandte Chemie International Edition

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ER -

An Efficient Method for the In Vitro Production of Azol(in)e-Based Cyclic Peptides

Abstract

Keywords

UN SDGs

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